A mild, general method for conversion of esters to amides

Basha, Anwer; Lipton, M. F.; Weinreb, Steven M.

doi:10.1016/s0040-4039(01)83457-2

Cited by 632 publications

(315 citation statements)

References 9 publications

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“…To construct the required enone moiety, the methyl ester of 13 was converted to a Weinreb amide (28), which reacted smoothly with vinylmagnesium bromide to give the corresponding enone. After cleavage of the triethylsilyl ether with fluoride ion, a DessMartin oxidation (29) yielded the desired diketone.…”

Section: Resultsmentioning

confidence: 99%

A nucleophile-catalyzed cycloisomerization permits a concise synthesis of (+)-harziphilone

Stark

Pekari

Sorensen

2004

Proc. Natl. Acad. Sci. U.S.A.

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Substantial structural transformations of much use in complex chemical synthesis can be achieved by channeling the reactivity of highly unsaturated molecules. This report describes the direct conversion of an acyclic polyunsaturated diketone to the HIV-1 Rev͞Rev-responsive element inhibitor harziphilone under mild reaction conditions. nucleophilic catalysis ͉ Baylis-Hillman reaction ͉ conjugate additions ͉ electrocyclizations ͉ domino reactions T he reactivity of activated polyenes is the basis for some of the most impressive structural transformations in nature and chemical synthesis. The biosyntheses of the complex structures of the polycyclic triterpenes from squalene and 2,3-oxidosqualene may be viewed as paragons for processes that build polycyclic molecular complexity directly from reactive polyenes (1-3). In connection with our efforts to channel the reactivity of activated polyunsaturated molecules, we sought mild reaction conditions under which compound 1 could be isomerized to the bicyclic structure of harziphilone (2), a naturally occurring inhibitor of the binding interaction between the HIV-1 Rev protein and the Rev-responsive element (RRE) of viral mRNA (4) (Scheme 1). This report describes an enantioselective synthesis of (ϩ)-harziphilone based on the general idea expressed in Scheme 1.The structure of (ϩ)-harziphilone (2) comprises fifteen carbon atoms, two six-membered ring systems, one carbocyclic and the other heterocyclic, a keto group, two contiguous hydroxylbearing stereocenters, and a pentadienyl side chain. All of the polar groupings of harziphilone are confined to the sixmembered carbocycle, whereas the hydrophobic pentadienyl moiety is displayed as a side chain on the ␣-pyran ring. Our approach to the problem of synthesizing this natural product was guided by the retrosynthetic analysis shown in Scheme 2.The independent early investigations of Büchi (5) and Marvell (6, 7) provided a sound basis for the proposal that the oxacyclic ring of harziphilone, with its particular arrangement of alkenes, could arise by a 6 -electrocyclization of a compound of type 3 (for selected examples of this type of valence isomerization in synthesis see refs. 8-11). With several electrophilic sites and a high degree of unsaturation, 3 was perceived to be a challenging objective for synthesis, and we elected to explore the possibility of producing this potentially transient intermediate in situ from a doubly activated, polyunsaturated acyclic compound of type 1. To implement this concept, we would seek a suitable heteroatom nucleophile that could attack the unsubstituted enone moiety in 1. Although almost certainly reversible, such a site-selective, intermolecular conjugate addition reaction could trigger an intramolecular conjugate addition (see arrows in 4), resulting in the production of a key carbon-carbon bond and the carbocyclic ring of (ϩ)-harziphilone (for selected tandem conjugate addition͞Michael cyclization reactions see refs. 12-17). A ␤-elimination of the heteroatom nucleophile might then genera...

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Section: Resultsmentioning

confidence: 99%

A nucleophile-catalyzed cycloisomerization permits a concise synthesis of (+)-harziphilone

Stark

Pekari

Sorensen

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…After condensation of carboxylic acid 60 with the chiral oxazolidinone moiety, N-acyloxazolidinone (61) was deprotonated with LDA and treated with aldehyde 62, which contained a phenylselenyl group as a masked double bond (prepared from (R)-(+)-a-hydroxybutyrolactone in three steps), to afford the syn-aldol product 63 as a single isomer. Straightforward transformation of alcohol 63 to the corresponding Weinreb amide [43] was achieved by using AlMe 3 ; subsequent TMS protection of the secondary alcohol and addition of a vinyl Grignard reagent afforded the divinyl species 64. RCM was effected by using the Grubbs first-generation catalyst [44] in the presence of [Ti-A C H T U N G T R E N N U N G (OiPr) 4 ], resulting in the formation of cyclohexenone 65 (53 % yield).…”

Section: Kims Synthesismentioning

confidence: 99%

Syntheses of Fumagillin and Ovalicin

Yamaguchi

Hayashi

2010

Chemistry A European J

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This review focuses on the synthetic strategies used for the construction of fumagillin, ovalicin, and other natural products of this family that are known angiogenesis inhibitors. These compounds are comprised of a cyclohexane framework, two epoxides, and five or six contiguous stereogenic centers. The first total syntheses of fumagillin and ovalicin were reported by Corey in 1972 and 1985, respectively. There were numerous studies directed at these natural products in the decades that followed with many reports appearing in the year 2000 or later. Despite the relatively small size of these molecules, their syntheses highlight the efficient construction of stereogenic centers in organic synthesis.

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“…Previous reports related to this type of transformations have appeared in the literature, but they have been only briefly investigated. 6,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Activation methods have found the reagents to be resistant to amide formation of 2-aminopyrimidines with low or moderate yields. [11][12][13][14] By the addition of the appropriate benzoyl chloride to 2-amino-4-(3-pyridinyl)pyrimidine in refluxing pyridine, 6 a group of N-mono-and N,N-dibenzoyl derivatives has been prepared in low yield.…”

Section: Introductionmentioning

confidence: 99%

“…6,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Activation methods have found the reagents to be resistant to amide formation of 2-aminopyrimidines with low or moderate yields. [11][12][13][14] By the addition of the appropriate benzoyl chloride to 2-amino-4-(3-pyridinyl)pyrimidine in refluxing pyridine, 6 a group of N-mono-and N,N-dibenzoyl derivatives has been prepared in low yield. The same mixture of N-monobenzoyland N,N-dibenzoyl-2-aminopyrimidines has been obtained (15% and 45%, respectively) by reaction of the 2-aminopyrimidine scaffold with benzoyl chloride in refluxing dichloromethane 15 and excess pyridine for 48 h. Peracylation of a 2,4-diaminopyrimidine-derivative has also been obtained with excess of benzoyl chloride in pyridine at room temperature for 18 hours, 16,17 while N,N-dibenzoyl-deoxycytidine has been formed as a by-product in the N-benzoylation of deoxycytidine 18 and 2-aminopyridines.…”

Section: Introductionmentioning

confidence: 99%

Insights into the N,N-diacylation reaction of 2-aminopyrimidines and deactivated anilines: an alternative N-monoacylation reaction

Théodorou¹,

Gogou²,

Giannousi³

et al. 2013

Arkivoc

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During the N-benzoylation reaction for the synthesis of N-substituted aminopyrimidines, an undesired N,N-diacylation reaction took place. The extension of this N-acylation reaction to a series of several 2-aminopyrimidines, aminopyrazines and highly deactivated anilines produced analogous results. The possible mechanism responsible for that behavior is investigated and an advantageous alternative procedure for the clean formation of the desired amides is suggested.

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A mild, general method for conversion of esters to amides

Cited by 632 publications

References 9 publications

A nucleophile-catalyzed cycloisomerization permits a concise synthesis of (+)-harziphilone

A nucleophile-catalyzed cycloisomerization permits a concise synthesis of (+)-harziphilone

Syntheses of Fumagillin and Ovalicin

Insights into the N,N-diacylation reaction of 2-aminopyrimidines and deactivated anilines: an alternative N-monoacylation reaction

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